The overall objective of this study is to obtain a better understanding of the details of the biosynthesis and assembly of the elastic fiber in the lung and the possible effect of alterations in this biosynthesis on the development of emphysema. The biosynthesis of the elastic fiber, which is composed of elastin and microfibrils, will be studied in embryonic rat lungs maintained in organ cultures for extended periods of time, as well as in lung fragments of other animals maintained in short term culture. The cultures will be incubated with radioactive amino acids and the labeled soluble precursor proteins of the fiber identified with specific antisera. The rates of synthesis and degradation will be measured under different experimental conditions. The interaction between purified microfibrils and tropoelastin will be examined to determine whether complex formation occurs between the two, and if so what is the nature of the bonding and stoichiometry. By using various inhibitors in the biosynthetic systems, we hope to ascertain whether there is a relationship between the synthesis of topoelastin and the microfibrillar protein. The degradation of the elastic fiber and its precursor components by a number of biologicaly significant proteases will be examined in detail in order to compare this degradation to the degradation of elastin found in experimental models of emphysema and to human emphysema. Since enzymes other than elastases, such as trypsin-like proteases, may be involved in the pathogenesis of emphysema, the effects of these proteases will be studied on the development of emphysema initiated by various doses of pancreatic elastase in a hamster model system. We seek a detailed picture of the pathogenesis of emphysema and specifically hope to learn whether interface in the biosynthesis of the elastic fiber, in contrast to degradation of the formed fiber, plays a significant role in the development of the disease. By the use of radioimmune assays, we shall attempt to identify peptides derived from elastin and elastin-specific antibodies in the sera of humans and experimental animals with emphysema, as a method of monitoring the disease.